fter an intravitreal dose of 2 mg.
Effects on male and female fertility were assessed as part of a 6-month study in monkeys with intravenous administration of aflibercept at doses ranging from 3 to 30 mg/kg. Absent or irregular menses associated with alterations in female reproductive hormone levels and changes in sperm morphology and motility were observed at all dose levels. Based on Cmax and AUC for free aflibercept observed at the 3 mg/kg intravenous dose, the systemic exposures were approximately 4,900-fold and 1,500-fold higher, respectively, than the exposure observed in humans after an intravitreal dose of 2 mg. All changes were reversible.
6. Pharmaceutical particulars
6.1 List of excipients
Polysorbate 20
Sodium dihydrogen phosphate, monohydrate (for pH adjustment)
Disodium hydrogen phosphate, heptahydrate (for pH adjustment)
Sodium chloride
Sucrose
Water for injection
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Store in a refrigerator (2°C to 8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
Prior to usage, the unopened vial of Eylea may be kept at room temperature (below 25°C) for up to 24 hours. After opening the vial, proceed under aseptic conditions.
6.5 Nature and contents of container
100 microlitres of solution in a vial (type I glass) with a stopper (elastomeric rubber), and an 18 G filter needle. Pack size of 1.
6.6 Special precautions for disposal and other handling
The vial is for single use only.
Since the vial contains more volume (100 microlitres) than the recommended dose (50 microlitres), a part of the volume contained in the vial has to be discarded prior to the administration.
The solution should be inspected visually for any foreign particulate matter and/or discolouration or any variation in physical appearance prior to administration. In the event of either being observed, discard the medicinal product.
For the intravitreal injection, a 30 G x ½ inch injection needle should be used.
Instructions for use of vials:
1.Remove the plastic cap and disinfect the outer part of the rubber stopper of the vial.
2. Attach the 18 G, 5-micron filter needle supplied in the carton to a 1-ml sterile, Luer-lock syringe.
3. Push the filter needle into the centre of the vial stopper until the needle is completely inserted into the vial and the tip touches the bottom or bottom edge of the vial.
4. Using aseptic technique withdraw all of the Eylea vial contents into the syringe, keeping the vial in an upright position, slightly inclined to ease complete withdrawal. To deter the introduction of air, ensure the bevel of the filter needle is submerged into the liquid. Continue to tilt the vial during withdrawal keeping the bevel of the filter needle submerged in the liquid.
5. Ensure that the plunger rod is drawn sufficiently back when emptying the vial in order to completely empty the filter needle.
6. Remove the filter needle and properly dispose of it.
Note: Filter needle is not to be used for intravitreal injection.
7. Using aseptic technique, firmly twist a 30 G x ½ inch injection needle to the Luer-lock syringe tip.
8. When ready to administer Eylea, remove the plastic needle shield.
9. Holding the syringe with the needle pointing up, chec |
